ejpmr, 2020,7(3), 497-505 SJIF Impact Factor 6.222 EUROPEAN JOURNAL OF PHARMACEUTICAL Review Article Pradnya et al. European Journal of Pharmaceutical and Medical Research AND MEDICAL RESEARCH ISSN 2394-3211

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A REVIEW ON DEVELOPMENT AND VALIDATION OF ULTRA PERFORMANCE LIQUID FOR ESTIMATION OF DRUG IN PHARMACEUTICAL DOSAGE FORM.

Pradnya G. Shelke*, Vijay S. Wakale and Ganesh Y. Dama

Department of Quality Assurance, Sharadchandra Pawar College of Pharmacy, Dumbarwadi (Otur), Tal-Junner, Dist- Pune 412409, Maharashtra, India.

*Corresponding Author: Pradnya G. Shelke Department of Quality Assurance, Sharadchandra Pawar College of Pharmacy, Dumbarwadi (Otur),Tal-Junner, Dist-Pune 412409, Maharashtra, India. Email Id: [email protected],

Article Received on 21/01/2020 Article Revised on 10/02/2020 Article Accepted on 01/03/2020

ABSTRACT In recent years, remarkable technological advances have been made in particle chemistry performance, system optimization, detector design, and data processing and control. When brought together, the individual achievements in each discipline have created a step-function improvement in chromatographic performance ultra performance liquid chromatography (UPLC) is a modern technique which gives a new direction for liquid chromatography. UPLC which enhance mainly three areas of liquid chromatography: speed, resolution, and sensitivity. UPLC system column containing bridged ethylsiloxane / silica hybrid (BEH) structure with fine particle size (less than 1.7 m) is utilized and particle less than 2μm in diameter to acquire better resolution, speed, and sensitivity compared with HPLC. In twenty first centenary pharmaceutical industries are focusing for new ways to in economy and shorten time for development of drugs and drug product. The separation and quantification in UPLC is done under very high pressure (up to 100m pa). As contrast to HPLC, under high pressure it is observed that not any negative influence on analytical column and also other components like time and solvent consumption is less in UPLC. The commence review article is an endeavor to offer pervasive awareness around the development and Validation details about the UPLC and related techniques with the aim on practice to an estimation of medicinal Active agents in the last 10 years. The article also focused on general overview of UPLC. Method development and validation of UPLC method for estimation of drug and drug product.

KEYWORDS: Drug, UPLC, HPLC, Resolution,

1. INTRODUCTION The Van Demeter curve governed by an equation with could be a field of study that three components shows that the usable flow range for a develops strategies, instruments and methods to get data good efficiency with small diameter particles is much on the composition and nature of matter. It is involved greater than for larger diameters The UPLC has involved with the chemical characterization of matter and the development of a new instrumental system for liquid therefore pharmaceutical analysis covers matter having chromatography, which can take advantage of the pharmaceutical applications.[1] UPLC refers to Ultra separation performance (by reducing dead volumes) and Performance Liquid Chromatography. It improves in 3 consistent with the pressures (about 8000 to 15,000 PSI, areas: activity resolution, speed and sensitivity analysis. compared with 2500 to 5000 PSI in HPLC).[5] Efficiency It uses fine particles and saves time and reduces solvent is proportional to column length and inversely consumption.[2] The UPLC relies on the principal of use proportional to the particle size18. Therefore, the column of stationary section consisting of particles but a pair of can be shortened by the same factor as the particle size μm. The underlying principles of this progress area unit without loss of resolution.[6] The application of UPLC ruled by the van Demeter equation, That is associate resulted in the detection of additional drug metabolites, formula that describes the connection between linear rate superior separation and improved spectral quality.[7] (flow rate) and plate height (HETP or column efficiency). UPLC comes from HPLC.[3] HPLC has been As particle size decreases to less than 2.5 m, there is a the evolution of the packing materials accustomed significant gain in efficiency and it’s doesn’t diminish at impact the separation.[4] increased linear velocities or flow rates according to the Van Deemter equation, common Van Deemter equation. By using smaller H = A + B/u + Cu, particles, speed and peak capacity can be expanded to new limits which is known as Ultra Performance.[8] The

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typical separation method is of HPLC (High temperatures b) use of monolithic columns. UPLC Performance Liquid Chromatography) with many presents the possibility to extend the utility of advantages like robustness, ease of use, good selectivity conventional HPLC, a widely used separation science. and adjustable sensitivity.[9] Its main limitation is the The ACQUITY UPLC System is the first instrument of want of efficiency compared to or its type to include Intelligent Device Management the capillary electrophoresis due to low diffusion technology.[13,14] coefficients in liquid phase, involving slow diffusion of analytes in the stationary phase.[10] The Van Deemter SMALL PARTICLE CHEMISTRY equation shows that efficiency extent with the use of The potential of the van Deemter equation cannot be smaller size particles but this leads to a rapid increase in fulfilled without smaller particles than those consistently back pressure, while most of the HPLC system can used in HPLC.[15] The design and development of sub-2 operate only up to 378 bars.[11] That is why short mm particles is a significant challenge, and researchers columns filled with particles of about 2 m are used with have been active in this area for some time to capitalize these systems, to accelerate the analysis without loss of on their advantages. Figure 1 shows Van Deemter plot, efficiency, while maintaining an acceptable loss of showing the progress of particle sizes over the last three load.[12] To improve the efficiency of HPLC separations, decades.[16] the following can be done: - a) work at higher

Fig 1: Van Deemter plot, illustrating the evolution of particle sizes over the last three decades.

Although high potency, non-porous one.5 millimetre These 1.7 millimetre particles derive their increased particles area unit commercially on the market, they mechanical stability by bridging the alkyl teams within suffer from poor loading capability and retention because the silicon oxide matrix. Packing 1.7 millimetre particles of low extent. UPLC must use novel porous particles that into consistent and rugged columns was additionally a can withstand high pressures. Silica based mostly challenge that required to be overcome.[19] In addition, at particles have smart mechanical strength, but can suffer high pressures; frictional heating of the mobile phase can from a number of disadvantages, which include a limited be quite significant and must be considered. With pH range and tailing of basic analytes.[17] In 2000, a column diameters generally employed in HPLC (3.0 to primary generation hybrid chemistry that took advantage 4.6 mm), a consequence of frictional heating is the loss of the simplest of each the silicon oxide and compound of performance due to temperature induced non uniform column worlds was introduced. Producing a classical sol- flow. To minimize the effects of resistance heating, gel synthesis that includes carbon within the style of smaller diameter columns (1–2.1 mm) area unit generally alkyl teams, these columns are mechanically strong, with used for UPLC.[20,21] high efficiency, and operate over an extended pH range.[18] But, so as to supply the sort of increased ADVANTAGES OF UPLC[22,23,24] mechanical stability needed for UPLC, a second Various advantages of UPLC are as follows generation bridged ethane hybrid (BEH) technology was • Decreases run time and increases sensitivity. developed. • Less solvent consumption

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• Provides the selectivity, sensitivity, and dynamic effects of high pressure. range of LC analysis.  In addition, the phases of less than 2 m are generally • UPLC’s fast resolving power quickly quantifies non-re generable and thus have limited use. related and unrelated compounds. • Faster analysis through the use of a novel separation INSTRUMENTATION material of very fine particle size. The schematic diagramme of UPLC and various parts of the instrument are shown in Figure1, and Figure 2, • Assures end-product quality, including final release respectively. testing. • Reduces process cycle times, so that more product Parts of ultra performance liquid chromatography can be produced with existing resources. (UPLC) • Delivers real-time analysis in step with  Solvent Reservoir manufacturing processes.  Degasser  High Pressure Pump DISADVANTAGES OF UPLC  Sample Injection Port  Due to increased pressure requires more  Column maintenance and reduces the life of the columns of  Detector these types. So far performances similar or even  Data Processing and Control higher have been demonstrated by using stationary  Waste phases of size around 2 m without the adverse

Fig 2: Schematic diagram of UPLC.

Fig. 3: UPLC instrument.

Analytical RP-UPLC method development validation play significant roles in the drug discovery Analytical RP-UPLC method development and development and manufacture of pharmaceuticals. These www.ejpmr.com 499 Pradnya et al. European Journal of Pharmaceutical and Medical Research

methods used to ensure the identity, purity, potency, & are known, the extent of dissociation and pH of a performance of drug products with speed, resolution, and solution of a monoprotic acid can be easily calculated.[31] sensitivity. There are many factors to consider when developing methods.[25] The method development start 2) UPLC Chromatographic conditions with collect the information about the analyte’s selection UPLC Column physicochemical properties (pKa, log P, solubility) and The heart of a UPLC system is the column. The Change detection mode would be suitable for analysis. The aim in column will have the greatest effect on the resolution of the RP-UPLC-method is to resolve and separatly of analytes during method development. Generally, the quantify the main active drug, any reaction impurities, all nature of stationary phase has the greatest effect on available synthetic inter-mediates and any capacity factor, selectivity, efficiency and . There degradants.[26,27] are several types of matrices for support of the stationary phase, including silica and polymers. Resolution is Steps involve in RP-UPLC method development are increased in a 1.7 µm particle packed column because 1. Understand the physicochemical properties of drug efficiency is better. Separation of the components of a molecule. sample requires a bonded phase that provides both 2. Set up RP-UPLC conditions. retention and selectivity. The UPLC separation available 3. Preparation of sample solution for method in Four bonded phases. C18 and C8 (straight chain alkyl development. columns), Shield RP18 (embedded polar group column) 4. Method optimization. and Phenyl (phenyl group tethered to the silyl 5. Validation of method. functionality with a C6 alkyl). Each column chemistry provides a unique combination of property, silanol 1) physicochemical properties of drug molecule activity, hydrolytic stability and chemical interaction The Physicochemical properties of a drug molecule play with analytes.[32,33] an important role in method development. For Method development one has to study the physicochemical C18 and C8 columns square measure thought-about the properties like molecular structure, molecular formula, universal columns of selection for many UPLC solubility, polarity, pKa and pH, of the drug molecule. separations by providing the widest hydrogen ion Polarity of analyte help, to decide the solvent and concentration vary. They incorporate tri practical matter composition of the mobile phase. In a nonpolar covalent bonding chemistries that manufacture superior low bond, the electrons are shared equally between two hydrogen ion concentration stability. This matter, atoms.[28] The solubility of drug molecule help for combined with a similar proprietary finish capping diluents selection. It work on principle, like dissolves processes because the C18 and C8 columns, provides like i.e., materials with similar polarity are soluble in long column lifetimes and excellent peak shape. This each other. Selection of diluents is based on the distinctive combination of matter and finish capping on solubility of analyte. The analyte must be soluble in the the one.7 m BEH particle creates a replacement diluents and must not react with any of the diluent dimension in property permitting a fast match to the components. The diluent should equivalent to the starting present HPLC column. An internal dimension (ID) of eluent composition of the assay to ensure that no peak two.1 metric linear unit column is employed. For deformation will occur, especially for early eluting maximum resolution, select a one hundred metric linear components.[29,30] unit length and for quicker analysis, and better sample turnout, choose 50 mm column. Conceptually, the pH and pKa plays an important role in UPLC method sensitivity increase for UPLC detection should be 2-3 development. The acidity or basicity of a substance is times higher than HPLC separations, depending on the defined most consistently by the pH value. Selecting a detection technique. MS detection is considerably proper pH for ionizable analytes often leads to increased by UPLC; raised peak concentrations with symmetrical and sharp peaks in UPLC. The acidity of an reduced action dispersion at lower flow rates promote aqueous solution is determined by the concentration of raised supply ionization efficiencies.[34,35] [H3O+] ions. Thus, the pH of a solution indicates the concentration of hydrogen ions in the solution. The Selection of Mobile Phase concentration of hydrogen ions can be indicated as [H+] The mobile phase is important part of liquid or its solvated form in as [H3O+] whose value normally chromatography. The aqueous and non aqueous solvent lies between 0 and 14. The lower the pH, the more acidic used in mobile phase. A buffer is a partly neutralised is the solution. The pH of a solution can be changed acid which counter changes in pH. Consideration of the simply by adding acid or base to the solution. The pKa is affect of pH on analyte retention, type of buffer to use, characteristic of a particular compound, and it inform and its concentration, solubility in the organic modifier how readily the compound gives up a proton. If the pH and its influence on detection are important in reversed- is known, the ratio may be calculated. This ratio is phase chromatography (RPC) method development of individualistic of the analytical concentration of the acid. ionic analytes. An inappropriate choice of buffer, in When the pKa and analytical concentration of the acid terms of buffering species, ionic strength and pH, can result in poor or unrepeatable retention and tailing in

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reverse-phase separation of polar and ionizable packing is pH 2 to 8. It is important that the buffer has a compounds.[36,37] pKa close to the desired pH since buffer controls pH best at their pKa. A rule is to choose a buffer with a pKa Buffer selection value <2 units of the desired mobile phase pH. Choice of buffer is typically governed by the desired pH. The typical pH range for reversed-phase on silica-based

Table 1: Buffer used for mobile phase. Buffer pKa Useful pH Range UV cutoff 4.8 3.8-5.8 Ammonium acetate 9.2 8.2-10.2 205(10mM) Ammonium hydroxide/ ammonia 9.2 8.2-10.2 KH2PO4/K2PO4 7.2 6.2-8.2 <200nm (0.1%) KH2PO4/ phosphoric acid 2.1 1.1-3.1 <200nm (0.1%) 210nm Potassium Acetate/ acetic acid 4.8 3.8-5.8 (10mM) 210nm Potassium formate/ formic acid 3.8 2.8-4.8 (10mM) 210nm Trifluoroacetic acid <2 1.5-2.5 (0.1%)

General considerations during buffer selection down to cut back potential band spreading. A fast 1. Mobile phases should be degassed. injection cycle time is required to completely exploit the 2. Phosphate is more soluble in methanol/water than in speed afforded by UPLC, that successively needs a high acetonitrile/water or THF/water. sample capability. Low volume injections with stripped- 3. Ammonium salts are generally more soluble in down carryover also are needed to extend sensitivity. organic/water mobile phases· There also are direct injection approaches for biological [39] 4. TFA can degrade with time, is volatile, absorbs at low samples. UV wavelengths. 5. Microbial growth can quickly occur in buffered Selection of detector mobile phases that contain little or no organic modifier. Detector is a very important part of HPLC. Selection of 6. At pH greater than 7, phosphate buffer accelerates the detector depends on the chemical nature of analytes, dissolution of silica and severely shortens the lifetime of potential interference, limit of detection needed, silica-based HPLC columns. If possible, organic buffers availableness and/or price of detector. For UPLC should be used at pH greater than 7. detection, the tunable UV/Visible detector is employed 7. Ammonium bicarbonate buffers usually are prone to which has new physical science and code to support pH changes and are usually stable for only 24 to 48 LAN communications at the high knowledge rates. hours. The pH of this mobile phase tends to become Conventional absorbance-based optical detectors square more basic due to the release of carbon dioxide. calculate concentration sensitive detectors, and for UPLC 8. After buffers are prepared, they should be filtered use, the flow cell volume would ought to be reduced in through a 0.2-μm filter. normal UV/Visible detectors to keep up concentration and signal. According to Beer’s Law, smaller volume Buffer concentration: Generally, a buffer concentration conventional flow cells would also bring down the path of 10-50 millimetre is adequate for little molecules. length upon which the signal strength depends. A Generally, no quite five hundredth organic ought to be reduction in cross-sectional means that the sunshine path used with a buffer. This will rely on the precise buffer is reduced, and transmission drops with increasing noise. likewise as its concentration. Phosphoric acid and its Therefore, if a standard HPLC flow cell were used, metal or metallic element salts square measure the UPLC sensitivity would be compromised. The foremost common buffer systems for reversed-phase ACQUITY Tunable UV/Visible detector cell consists of HPLC. Phosphonate buffers are often replaced with salt a light guided flow cell equivalent to an optical fiber. buffers once analyzing insecticide compounds.[38] Light is expeditiously transferred down the flow cell in an inside coefficient mode that also maintains a 10mm SAMPLE INJECTION flow cell path length with a volume of solely 500mL. In UPLC, sample introduction is critical Conventional injection valves, either automatic or manual, don't seem Tubing and connections within the system square to be designed and hardened to figure at extreme measure expeditiously routed to keep up low dispersion pressure. To protect the column from extreme pressure and to require advantage of leak detectors that act with fluctuations, the injection method should be the software system to alert the user to potential comparatively pulse-free and therefore the the} problems. sweptwing volume of the device also must be stripped- www.ejpmr.com 501 Pradnya et al. European Journal of Pharmaceutical and Medical Research

Preparation of sample solutions for method experimentally to lay out a quantitative system suitability development test report in that number of theoretical plates, capacity Sample preparation is a censorious step of method factor, relative retention time, resolution, tailing factor, development that the analyst must explore. The drug relative standard deviation (precision). These are substance being analyzed should be stable in diluent. In measured on a peak or peaks of known retention time initial UPLC method development, preparations of the and peak width.[44,50] solutions in amber flasks should be performed till it is determined that the active component is stable at room Specificity temperature and does not degrade under normal The Specificity of analytical procedure is the ability to laboratory conditions. The sample solution should be assess unequivocally the analyte in the presence of filtered; the use of a 0.22 or 0.45 μm pore-size filter is components which may be expected to be present. recommended for removal of particulates size more than Typically these might include impurities, degradants, 0.45 μm. Filtration is a preventive maintenance tool for matrix, etc. Identification in analytical procedure to HPLC analyses.[40] ensure the identity of an analyte. Purity Tests in analytical procedure to ensure that all the analytical The effectiveness of the syringe filters is largely procedures performed allow an accurate statement of the determined by their ability to remove content of impurities of an analyte, i.e. related contaminants/insoluble components without leaching substances, residual solvents, heavy metals etc.[45,50] undesirable artifacts (i.e., extractables) into the filtrate. If any additional peaks are observed in the filtered samples, Linearity then the diluent must be filtered to determine if a The linearity is definded as the ability of obtain test leachable component is coming from the syringe filter results which are directly proportional to the housing/filter. concentration of analyte in the analytical procedure. If there is a linear relationship, test results should be Method Validation evaluated by appropriate statistical methods, for Validation of an analytical procedure is the process of example, by calculation of a regression line by the establishing documentary evidence demonstrating that a method of least squares. In some cases, to obtain procedure, process, or activity carried out in testing and linearity between assays and sample concentrations, the then production maintains the desired level of test data may need to be subjected to a mathematical compliance at all stages requirements for its intended transformation prior to the regression analysis. For the use. It should describe in detail the steps necessary to establishment of linearity, a minimum of 5 perform each analytical test.[41] The methods validation concentrations is recommended. Other approaches process for analytical procedures begins with the planned should be justified. The correlation coefficient, y- and systematic collection by the applicant of the intercept, slope of the regression line and residual sum of validation data to support analytical procedures. All squares should be submitted. A plot of the data should be analytical methods that are intended to be used for included. In addition, an analysis of the deviation of the analyzing any drug samples will need to be validated. actual data points from the regression line may also be The validation of analytical methods is done as per ICH helpful for evaluating linearity.[46,50] guidelines.[42,43] Accuracy Components of method validation The accuracy of an analytical procedure expresses the The following are typical analytical performance closeness of agreement between the worth which is characterstics which may be tested during methods accepted either as a standard true value or an accepted validation. reference value and the value found. The accuracy of  System suitability determination analytical procedure to synthetic mixtures of the drug  Specificity product components to which known quantities of the  Linearity drug substance to be analysed are added. In cases  Accuracy where it's impossible to get samples of all drug product  Precision components, it's going to be acceptable either to  Repeatability feature known quantities of the analyte to the drug  Intermediate precision product or to match the results obtained from a second,  Detection limit well characterized procedure, the accuracy of which is  Quantitation limit stated and/or defined. Accuracy could also be inferred  Robustness once precision, linearity and specificity are established.[47,48] System Suitability Determination System Suitability Determination is the evaluation of the Precision components of an analytical system to show that the The precision of an analytical procedure expresses the performance of a system meets the standards required by closeness of agreement between a series of a method. These Determination can be calculated measurements obtained from multiple sampling of an

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equivalent homogeneous sample under the prescribed In the case of liquid chromatography, examples of conditions. Precision could also be considered at three typical variations are: levels: repeatability, intermediate precision and - influence of variations of pH in a mobile phase; reproducibility. Precision should be investigated using - influence of variations in mobile phase composition; homogeneous, authentic samples. However, if it's - different columns (different lots and/or suppliers); impossible to get a homogeneous sample it's going to be - temperature; investigated using artificially prepared samples or a - flow rate. sample solution. The precision of an analytical procedure is typically expressed because the variance, variance or CONCLUSION coefficient of variation of a series of measurements.[49,50] This review describes the general technique of UPLC method development and validation of analytical i) Repeatability- Repeatability expresses the precision method. The approach for the UPLC method under an equivalent operating conditions over a brief development for the separation of pharmaceutical interval your time. Repeatability is also termed intra compounds was discussed. UPLC by using 2 µm particle assay precision.[50] size gives increased resolution, speed and sensitivity for liquid chromatography. The UPLC method is a reduction ii) Intermediate precision- The extent to which of analysis time, along with reduced solvent intermediate precision should be established depends on consumption, high throughput analysis and reduction in the circumstances under which the procedure is intended cost of analysis. From the literature survey of UPLC to be used. The applicant should establish the method development and validation it can be concluded consequences of random events on the precision of the that all categories of pharmaceutical drugs can be analytical procedure. Typical variations to be studied analyzed by UPLC method within a very short period of include days, analysts, equipment, etc. It is not needed to time and with less solvent consumption. UPLC increases review these effects individually. The use of an and expands the significance of chromatography. It is experimental design is inspired.[50] transforming lives and laboratories, creating new opportunities for business profitability, and bringing new iii) Reproducibility- Reproducibility is assessed by meaning to quality. The literature survey shows that means of an inter-laboratory trial. Reproducibility should research on UPLC method development and validation, be considered just in case of the standardisation of an both, at national and international level have been analytical procedure, as an example.[50] successfully done on all categories of drugs.

6) Detection limit- The detection limit of an individual REFERENCES analytical procedure is the lowest amount of analyte in a 1. Wu N. Lippert J A. Lee M.L. Practical aspects of sample which can be detected but not necessarily ultrahigh pressure capillary liquid chromatography quantitated as an exact value.[50] J. Chromotogr, 2001; 1: 911. 2. Van Deemter J J. Zuiderweg E J. Klinkenberg A. 7) Quantitation limit- The quantitation limit of an Longitudinal diffusion and resistance to mass individual analytical procedure is the lowest amount of transfer as causes of non ideality in chromatography. analyte in a sample which can be quantitatively Chem. Eng. Sci., 1956; 5: 271–289. determined with suitable precision and accuracy. The 3. Srivastava B. Sharma B K. Baghel U S. UPLC: a quantitation limit is a parameter of quantitative assays chromatographic technique. Inter J of Pharmaceu for low levels of compounds in sample matrices, and is Quality Assu, 2010; 2(1): 19-25. used particularly for the determination of impurities 4. Unger K K. Kumar D. Grun M. Buchel G. Ludtke S. and/or degradation products.[50] Adam T. Scumacher K. Renker S. J. Chromatogr A, 2000; 892: 47-55. 8) Robustness - The evaluation of robustness should be 5. Swartz M E. UPLC: An Introduction and Review. J considered during the development phase and depends of Liq Chromato & Related Techno, 2005; 28: on the type of procedure under study. It should show the 1253–1263. reliability of an analysis with respect to deliberate 6. Kondawar M S, Patil S B, Bhise S B et al. ―Ultra variations in method parameters. If measurements are Performance Liquid Chromatography: A Faster and susceptible to variations in analytical conditions, the Sensitive Method over HPLC‖ [online].2006 [cited analytical conditions should be suitably controlled or a 2006 oct 24] Available from: URL: precautionary statement should be included in the http://www.pharmainfo.net/volumes-and- procedure. One consequence of the evaluation of issues/2006/vol-4-issue-5. robustness should be that a series of system suitability 7. Swartz M. Murphy B J. Sievers D. UPLC: parameters (e.g., resolution test) is established to ensure Expanding the limits of HPLC. GIT Lab J, 2004; that the validity of the analytical procedure is maintained 8(5): 43-45. whenever used.[50,51] 8. Swartz M E. UPLC: Tomorrow’s HPLC technology today. Lab plus Int, 2004; 18(3): 6-9. 9. Nguyen D T. Guillarme D. Rudaz S. Veuthey J L.

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Fast analysis in liquid chromatography using small their epimers in liquid hog manure using Ultra particle size and high pressure. J Sep Sci, Aug 2006; Performance Liquid Chromatography with UV 29(12): 1836-48. detection. Chemosphere, Jan 2010; 78(4): 353–359. 10. Gaikwad P. Sawant S. Ghante M. Munot N. Ultra 21. Chen L. Qin F. Ma Y. Li F. Quantitative performance liquid chromatography: A recent novel determination of azithromycin in human plasma by development in HPLC. Inter J of Compre Pharm, ultra performance liquid chromatography–electro 2010; 2(08): 1-3. sprays ionization mass spectrometry and its 11. Butle S R. Kalyankar T M. Chidrawar R D. Review application in a pharmacokinetic study. J of on ultra performance liquidchromatography: an Chromato B, 15 August 2007; 855(2): 255–261. eminent, sensitive and high throughput analysis over 22. Cai S. Huo T. Feng W. Chen L. Qin F. Ma Y. Li F. hplc. Quantitative determination of mitiglinide in human 12. Trivedi R K. Patel M C. Jadhav S B. A Rapid, plasma by ultra-performance liquid Stability Indicating RP-UPLC Method for chromatography/electrospray ionization tandem Simultaneous Determination of Ambroxol mass spectrometry. J of Chromato B, 1 June 2008; Hydrochloride, Cetirizine Hydrochloride and 868(1–2): 83–87. Antimicrobial Preservatives in Liquid 23. Loos W. Graan A. Bruijn P. Schaik R. Simultaneous Pharmaceutical Formulation. Sci Pharm, 2011; 79: quantification of dextromethorphan and its 525–543. metabolites dextrorphan, 3-methoxymorphinan and 13. Yadava M. Rao R. Kurania H. Singhala P. 3-hydroxymorphinan in human plasma by ultra Goswamia S. Shrivastav P S. Application of a rapid performance liquid chromatography/tandem triple- and selective method for the simultaneous quadrupole mass spectrometry Pharm Biomed Anal, determination of protease inhibitors, lopinavir and 25 January 2011; 54 (2): 387–394. ritonavir in human plasma by UPLC–ESI-MS/MS 24. Sahu K. Karthikeyan C. Moorthy N. Trivedi P. A for bioequivalence study in Indian subjects. J of Validated UPLC Method Used for the Pharm Biomed Anal, 2009; 49: 1115–1122. Determination of Trandolapril and its Degradation 14. Wang D. Jiang K. Yang S. Qin F. Lu X. Li F. Products as per ICH Guidelines. Current Pharmaceu Determination of nifedipine in human plasma by Ana, August 2011; 7(3): 182-188. ultra performance liquid chromatography–tandem 25. Maggio, R.M., Vignaduzzo, S.E. and Kaufman, mass spectrometry and its application in a T.S., 2013. Practical and regulatory considerations pharmacokinetic study. J of Chromato B, 15 June for stability-indicating methods for the assay of bulk 2011; 879(20): 1827–1832. drugs and drug formulations. TrAC Trends in 15. Berg T. Lundanes E. Christophersen A. Strand D. Analytical Chemistry, 49: 57-70. Determination of opiates and cocaine in urine by 26. Gupta, H., Aqil, M., Khar, R.K., Ali, A., Sharma, A. high pH mobile phase reversed phase UPLC– and Chander, P., 2010. Development and validation MS/MS. Jour of Chromato B, Feb 2009; 877(4): of a stability-Indicating RP-UPLC method for the 421–432. quantitative analysis of sparfloxacin. Journal of 16. Arthur L. Rochat B. Pesse B. Mercier T. Tissot F. chromatographic science, 48(1): 1-6. Multiplex UPLC-MS method for simultaneous 27. Krishnaiah, C., Reddy, A.R., Kumar, R. and quantification in human plasma of Fluconazole, Mukkanti, K., 2010. Stability-indicating UPLC Itraconazole, Hydroxyitraconazole, Posaconazole, method for determination of Valsartan and their Voriconazole, Voriconazole-N-Oxide, degradation products in active pharmaceutical Anidulafungin, and Caspofungin. Antimicrobial ingredient and pharmaceutical dosage agents and chemo, Dec. 2010; 54(12): 5303–5315. forms. Journal of pharmaceutical and biomedical 17. Stolker A. Rutgers P. Oosterink E. Lasaroms J P. analysis, 53(3): 483-489. Peter R. Comprehensive screening and 28. Hansen, N.T., Kouskoumvekaki, I., Jørgensen, F.S., quantification of veterinary drugs in milk using Brunak, S. and Jónsdóttir, S.O., 2006. Prediction of UPLC–ToF-MS. Anal Bioanal Chem, July 2008; pH-dependent aqueous solubility of druglike 391(6): 2309. molecules. Journal of chemical information and 18. Verplaetse R. Development and validation of a modeling, 46(6): 2601-2609. sensitive UPLC–MS/MS method for the analysis of 29. Gupta, V., Jain, A.D.K., Gill, N.S. and Gupta, K., narcotic analgesics in urine and whole blood in 2012. Development and validation of HPLC forensic context. Forens Sci Inter, 26 February 2011. method-a review. Int. Res J Pharm. App Sci, 2(4): 19. Seshadri R. Desai M. Raghavaraju T. Krishnan D. 17-25. Rao D. Chakravarthy I. Simultaneous Quantitative 30. Ruta, J., Rudaz, S., McCalley, D.V., Veuthey, J.L. Determination of Metoprolol, Atorvastatin and and Guillarme, D., 2010. A systematic investigation Ramipril in Capsules by a Validated Stability- of the effect of sample diluent on peak shape in Indicating RP-UPLC Method. Sci Pharm, 2010; 78: hydrophilic interaction liquid 821–834. chromatography. Journal of chromatography 20. Tylova T. Olsovska J. Novak P. Flieger. High- A, 1217(52): 8230-8240. throughput analysis of tetracycline antibiotics and 31. Jones, J.R., 1986. Carbon acid reactivity. Annual

www.ejpmr.com 504 Pradnya et al. European Journal of Pharmaceutical and Medical Research

Reports Section" C"(Physical Chemistry), 83: diagnostic tests that depend on nucleic acid 197-209. amplification and detection. Journal of Clinical 32. Makarov, A., LoBrutto, R., Karpinski, P., Virology, 56(3): 344-354. Kazakevich, Y., Christodoulatos, C. and Ganguly, 43. Laghave, P.K. and Gite, S.V., 2017. An Overview A.K., 2012. Investigation of the effect of pressure on Validation Technique. Journal of Current and liophilic mobile phase additives on retention of Pharma Research, 8(1): 2249-2254. small molecules and proteins using reversed-phase 44. Yadav, S.B., Bravoco, R.R., Chatfield, A.T. and ultrahigh pressure liquid chromatography. Journal of Rajkumar, T.M., 1988. Comparison of analysis liquid chromatography & related techniques for information requirement technologies, 35(3): 407-427. determination. Communications of the ACM, 31(9): 33. LoBrutto, R., Makarov, A., Jerkovich, A., McGill, 1090-1097. R., Kazakevich, Y. and Vivilecchia, R., 2008. 45. Bakshi, M. and Singh, S., 2002. Development of Enhancing productivity in the analytical laboratory validated stability-indicating assay methods— through the use of ultra fast-HPLC in critical review. Journal of pharmaceutical and preformulation/formulation development. Journal of biomedical analysis, 28(6): 1011-1040. Liquid Chromatography & Related 46. Rozet, E., Ceccato, A., Hubert, C., Ziemons, E., Technologies®, 31(15): 2253-2285. Oprean, R., Rudaz, S., Boulanger, B. and Hubert, P., 34. Pyrzynska, K. and Sentkowska, A., 2015. Recent 2007. Analysis of recent pharmaceutical regulatory developments in the HPLC separation of phenolic documents on analytical method validation. Journal food compounds. Critical Reviews in Analytical of Chromatography A, 1158(1-2): 111-125. Chemistry, 45(1): 41-51. 47. Powell, C.J. and Seah, M.P., 1990. Precision, 35. Perryman, M., Hainaut, O., Dravins, D., Léger, A., accuracy, and uncertainty in quantitative surface Quirrenbach, A., Rauer, H., Kerber, F., Fosbury, R., analyses by Auger‐electron spectroscopy and x‐ray Bouchy, F., Favata, F. and Fridlund, M., 2005. photoelectron spectroscopy. Journal of Vacuum Report by the ESA-ESO Working Group on Extra- Science & Technology A: Vacuum, Surfaces, and Solar Planets. arXiv preprint astro-ph/0506163. Films, 8(2): 735-763. 36. McCalley, D.V., 2010. The challenges of the 48. Borman, Phillip, and David Elder. "Q2 (R1) analysis of basic compounds by high performance validation of analytical procedures." ICH Quality liquid chromatography: some possible approaches Guidelines, 2017; 127-166. for improved separations. Journal of 49. Rozet, E., Ceccato, A., Hubert, C., Ziemons, E., Chromatography A, 1217(6): 858-880. Oprean, R., Rudaz, S., Boulanger, B. and Hubert, P., 37. Davies, N.H., Euerby, M.R. and McCalley, D.V., 2007. Analysis of recent pharmaceutical regulatory 2008. Analysis of basic compounds by reversed- documents on analytical method validation. Journal phase high-performance liquid chromatography of Chromatography A, 1158(1-2): 111-125. using hybrid inorganic/organic phases at high 50. Guideline, ICH Harmonised Tripartite. "Text on pH. Journal of Chromatography A, 1178(1-2): validation of analytical procedures." In International 71-78. Conference on Harmonization, Geneva, 1994; 1-5. 38. Schiff, L., KUMPE, M. and STEWART, P., 1947. 51. Shabir, Ghulam A. "Validation of high-performance GASTRIC (AND SALIVARY) EXCRETION OF liquid chromatography methods for pharmaceutical RADIOIODINE IN MAN analysis: Understanding the differences and (PRELIMINARY. Journal of the National Cancer similarities between validation requirements of the Institute, 7(5): 349. US Food and Drug Administration, the US 39. Mousa Alreshidi, M. "Metabolomic and proteomic Pharmacopeia and the International Conference on responses of Staphylococcus aureus to changes in Harmonization." Journal of chromatography A, 987, the environmental conditions." PhD diss., School of 2003; 1-2, 57-66. Environmental and Life Sciences, University of Newcastle, Australia, 2015. 40. Jatto, E. and Okhamafe, A.O., 2002. An Overview of Pharmaceutical Validation and Process Controls in Drug Development. Tropical Journal of Pharmaceutical Research, 1(2): 115-122. 41. Prazeres, D.M.F. and Ferreira, G.N.M., 2004. Design of flowsheets for the recovery and purification of plasmids for gene therapy and DNA vaccination. Chemical Engineering and Processing: Process Intensification, 43(5): 609-624. 42. Saunders, N., Zambon, M., Sharp, I., Siddiqui, R., Bermingham, A., Ellis, J., Vipond, B., Sails, A., Moran-Gilad, J., Marsh, P. and Guiver, M., 2013. Guidance on the development and validation of

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